Fabrication Of Composite Microspheres And Fibers Via Electrospraying Method For Drug Carriers

Electrospraying method is a novel processing technique to fabricatepolymeric microspheres or micro/nanofibers from electrically charged liquidjets of polymer solutions or melts under high voltage electrostatic field.Recently, electrosprayed microspheres and fibers have been widely used in thebiomedical area. However, the surface of the electrosprayed microsphere isuncontrollable, and single polymeric drug-loaded microspheres have thedisadvantages of fast and uncontrollable drug release profiles. Moreover, thefabrication of composite microspheres is much more difficult. Thus, this papersystematically investigated the fabrication of biodegradable microspheres viaelectrospraying technique, produced organic/inorganic compositemicrospheres as anti-adhesion coating and drug carriers, and furtherinvestigated the properties of electrosprayed composite fibers as drug-carriers.In this study, biodegradable poly (L-lactide)(PLLA) was used toinvestigate the electrosprayed microspheres’ characterization, such asmorphology, size, size distribution, surface distribution of chemical elements,and surface charge, and systematically investigated the influence of differentelectrospraying parameters (solution concentration, jet voltage, flow rate, andcollecting distance) on the size and zeta potential of microspheres. The resultsdemonstrated that the surface groups of electrosprayed microspheresrearranged during electrospraying process: lower binding energy groups(methyl group) enriched on surface of the microspheres and higher bindingenergy groups (methine groups and ester groups) distributed in the subsurface.Of all the electrospraying parameters investigated, the size and zeta potential of the PLLA microspheres increased with the increase of solutionconcentration and flow rate, and decreased with the increase of injectionvoltage and collecting distance.In this study, a novel superhydrophobic biodegradable coating withconvex and concave micro-structures was fabricated by co-solventelectrospraying of poly-(L-lactide)(PLLA) and modified silica nanoparticles(MSN), investigating the surface hydrophilicity and anti-adhesion of cells andbacteria to the coating. The results manifested that the convex and concavemicro-structure by wrapping MSNs in the PLLA particles via co-solventelectrospraying resulted in the high roughness and hydrophobicity of theelectrosprayed PLLA/MSN coating. Besides the enrichment of lower bindingenergy groups (methyl groups) on the surface of electrosprayed particlesduring electrospraying process resulted in the superhydrophobicity of theelectrosprayed PLLA/MSN composite coating. The results of cells andbacteria adhesion demonstrated that electrosprayed PLLA/MSN compositecoating showed good anti-adhesion to cells and bacteria.In this study, PLLA and ibuprofen-loaded modified mesoporous silicas(MMS-IBU) composite microspheres were further fabricated via co-solventelectrospraying techniques, investigating the influence of the content of MMS-IBU and IBU on the release profiles of drug. The results indicated that theelectrosprayed PLLA-MMS-IBU composite microspheres have much slowerrelease rate compared with the electrosprayed PLLA-IBU microspheres, andreleased about15%-30%loaded-drugs in20days. Besides, the resultsdemonstrated that the drug release profiles could be controlled by the contentof MMS-IBU and IBU.It is the first time to fabricate poly (L-lactide)(PLLA) and MMS-IBUcomposite nanofibers through co-solvent electrospinning. The resultsdemonstrated that co-solvent electrospinning is an effective method to fullywrapped MMS-IBU in the PLLA fibers with convex and concave micro-structure on the surface. The drug release profile showed that the PLLA-MMS-IBU composite fibers had lower initial burst and long-term (more than100days) drug release. In animal studies, both PLLA-IBU and PLLA-MMS-IBU showed improved anti-adhesion properties and anti-inflammatory effectscompared to PLLA fibrous membrane alone after4weeks of implantation.Further, animals implanted with PLLA-MMS-IBU for8weeks showed thelowest inflammation and best recovery compared to those implanted withPLLA-IBU and PLLA, most likely as a result of its sustained release of IBUfrom electrospun PLLA-MMS-IBU composite fibers, while the electrospunPLLA-IBU fibers had completely released ibuprofen.In conclusion, this study systematically investigated the relationship ofsurface properties with electrospraying parameters under experimental studyand theoretical analysis, fabricated PLLA and silica nanoparticles compositemicrospheres and composite fibers via electrospraying method andinvestigated their application in biomedical area. This study provided a novelplatform technique to produce composite microspheres and composite fibers,and laid the foundation of the application of electrospraying method inbiomedical area.